An unexpectedly high percentage of included patients had troponin T elevations, which could be corroborated by electrocardiographs in only four cases suggesting that a high percentage of critically ill patients with a history of CAD suffer from clinically unrecognised (minor) myocardial damage.

Ciprofloxacin in low doses is, in volunteers, effective for decontaminating the digestive tract [elimination of aerobic Gram-negative bacilli (GNB)] without disturbing colonization resistance. Before using this concept in neutropenic patients, we investigated if a low dose quinolone is still effective when the colonization resistance is disturbed by another antimicrobial agent. Ciprofloxacin 20 mg daily was effective in eliminating Gram-negative bacilli from the digestive tract in 4/5 volunteers, in 1 volunteer the GNB persisted in low concentration. No colonization with exogenous resistant GNB occurred. Following impairment of colonization resistance by addition of clindamycin 300 mg daily, 3/5 volunteers became colonized by spontaneously acquired exogenous GNB resistant to ciprofloxacin. We conclude that selective decontamination with a quinolone in low dosage cannot be recommended in neutropenic patients because there is, in the case of disturbed colonization resistance, a real risk of acquisition of quinolone-resistant strains.

Superinfections originating from a digestive tract colonized by abnormally high concentrations of aerobic microorganisms as a result of impaired resistance to colonization (CR) may complicate antibiotic therapy. In this study, patients with a moderate to severe systemic infection were randomized to receive either cefotaxime (CTX, n = 10) or cotrimoxazole (CTR, n = 10), 2 antibiotic regimens presumed to spare CR; or imipenem/cilastine (I/C, n = 19). The effect on CR was measured indirectly by comparing the aerobic faecal flora before antibiotic treatment with that on day 8 of treatment. An increase in aerobic faecal flora denotes a disturbed CR, whereas a decrease means that the organism is sensitive to the effective faecal concentration of the antibiotic. Imipenem/cilastine-treated patients showed a significant increase in enterococci and Candida spp., while the number of aerobic Gram-negative rods remained constant. Cefotaxime-treated patients had evidence of an increase in enterococci, but not of Candida spp., and Escherichia coli numbers decreased significantly. In these patients the concentration of other Gram-negative aerobic rods showed a slight increase in 6 patients with a resistant Pseudomonas strain. Cotrimoxazole-treated patients showed a significant decrease in aerobic Gram-negative rods, a significant increase in Candida spp. and no change in enterococci. It is concluded that all 3 antimicrobial agents impair colonization resistance. Whether or not this is followed by overgrowth with resistant micro-organisms depends on the active faecal concentration of the antimicrobial agent and the MIC of the aerobic micro-organisms. The risk of overgrowth of the bowel with resistant Gram-negative bacilli appears to be smaller following cotrimoxazole than following cefotaxime or imipenem/cilastine.

Pefloxacin (400 mg twice daily) was administered orally for infection prophylaxis in neutropenic patients. Diffusible fecal pefloxacin concentration was determined by bioassay during 24 neutropenic periods. The median diffusible fecal pefloxacin concentration was 187 g/g. This concentration was comparable with those found in volunteers following oral and intravenous administration of pefloxacin (400 mg twice daily) (median of 171 and 155 g/g, respectively). From this study, it is concluded that pefloxacin administered orally results in a predictable high diffusible fecal concentration which leads to effective elimination of susceptible aerobic gram-negative bacilli from the colonic flora.Fluorinated carboxyquinolones are widely used for infection prophylaxis in patients with severe neutropenia (2, 4). These agents have a broad spectrum of activity against aerobic gramnegative bacilli (GNB) (including Pseudomonas aeruginosa) and are effective in preventing infections by gram-negative organisms (1,5,7,(10)(11)(12)18).Long-term prophylaxis of infection in patients with neutropenia may be achieved by elimination of potentially pathogenic aerobic flora from the digestive tract (3). In order to be effective, antibiotics used for decontamination of the digestive tract must reach high and predictable concentrations in the bowel (15). It has been suggested that nonabsorbable antimicrobial agents are required for this purpose (4). In volunteers, however, we observed high antimicrobial activity of pefloxacin in feces after oral (almost complete resorption) and intravenous administration of pefloxacin (16,17).In the present study, we investigated the diffusible fecal concentration of pefloxacin and eradication of GNB from feces in neutropenic patients following oral administration. We compare these results with those of similar previous studies in healthy volunteers following oral and intravenous administration (16,17).During 24 periods of chemotherapy-induced neutropenia, prophylactic antibiotics, including pefloxacin (400 mg twice a day [BID] orally), fluconazole (50 mg orally), amphotericin B (450 mg BID orally), and trimethoprim (2%, as nasal ointment), were given to decontaminate the digestive tract.All 13 patients (median age, 51 years; range, 49 to 76 years) were treated for a hematologic malignancy, and median duration of neutropenia (Ͻ500 neutrophils per l) was 16 days (range, 9 to 35). During the prophylaxis, no salads were permitted. Fecal samples were taken at admission and twice weekly to determine the diffusible pefloxacin concentration and to perform viable counts of aerobic GNB.The diffusible fecal concentration of pefloxacin was determined by an agar diffusion method. An undiluted aliquot of feces was put in a well (depth, 5 mm; diameter, 7 mm; volume, 0.77 ml) in a solid medium of Iso-Sensitest agar (300 ml; Oxoid, Basingstoke, United Kingdom) seeded with a strain of Escherichia coli (ATCC 25922). The MIC of pefloxacin for this strain is 0.25 g/ml. The diameters of the inhibition zones were compared with t...

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